Microelectromechanical Systems (MEMS) are machines fabricated on a microscopic scale using surface micromachining or LIGA processes. MEMS devices can include moveable members (e.g., gears, rotors, linkages, levers, hinges and mirrors) for applications including sensing (e.g., acceleration or chemicals), switching (electrical or optical signals) and optical display (e.g., moveable mirrors) functions. MEMS devices can further include actuators or motors for driving gear trains to perform various functions including coded locks and self-assembling structures.
In recent years, the design possibilities of microelectromechanical systems (MEMS) have expanded as the field has further matured. Recent advances in single crystal silicon wafer manipulation, the addition of integrated circuits as a practical modality for controlling these microstructures as well as other associated technologies has widened the horizon of possible uses (Senturia, S. D., et al., (1992) “A Computer-Aided Design System for Microelectromechanical Systems (MEMCAD)” Journal of Microelectromechanical Systems 1(1):3; Clerc, P-A., et al., (1998) “Advanced deep reactive ion etching: a versatile tool for microelectromechanical systems” J. Micromech. Microeng. 8(4):272-278; Petersen, K. E., (1998) “Toward Next Generation Clinical Diagnostic Instruments Scaling and New Processing Paradigms” Biomedical Microdevices 1 (1):71-79). One of the most promising novel aspects of this field is the design of MEMS which modulate and manipulate the small scale world of individual cells, thus facilitating, for the first time, an actual hands-on method for addressing biological issues at the level of the most basic unit of order in multicellular organisms.
Whereas many cells in the body are of a size on the order of a few microns, there is a special class of cells, the female gamete called the oocyte, which is far larger, on the order of 100 microns. Further, these cells, in many animals from sea urchins to mammals, are surrounded by a five to twenty micron thick selectively permeable glycoprotein coat called the Zona Pellucida.
The modification of the surface of the glycoprotein coating of oocytes and embryos is a desirable operation in endeavors such as the labeling of a great many of oocytes and embryos in the animal husbandry industry.
Further, the delivery of and removal of materials into and out of the cytoplasm of oocytes is a desirable operation in endeavors such as the generation of transgenic animals, intracytoplasmic sperm injection, assisted hatching, enucleation, nuclear transfer, and cytoplasmic transfer. At present the outcome of these procedures, being technically demanding and relatively novel and as such, not optimized, is very poor. The generation of transgenic animals born by way of microinjection of pronuclei offers very low percentages of actual transgenic animals but the applications for transgenic animals offers great promise (Wagner J, et al., (1995) “Transgenic animals as models for human disease” Clin Exp Hypertens 1995 May; 17(4):593-605; Woychik R P, and Alagramam K, (1998) “Insertional mutagenesis in transgenic mice generated by the pronuclear microinjection procedure” Int J Dev Biol 42(7 Spec No): 1009-17; Ebert K. M., (1998) “The use of transgenic animals in biotechnology” Int J Dev Biol 1998; 42(7 Spec No):1003-8). The use of intracytoplasmic sperm injection (ICSI), the placement of a sperm into the cytoplasm of an oocyte using a microinjection pipette, can be found in both animal husbandry as well as in human assisted reproduction (Joris H, et al. (1998) “Intracytoplasmic sperm injection: laboratory set-up and injection procedure” Hum Reprod 13 Suppl 1:76-86). Being a relatively new procedure, not all human assisted reproduction clinics offer ICSI as an option but studies have shown that it can offer significant advantages to those couples suffering from male factor infertility (Palermo G. D., et al. (1996) “Intracytoplasmic sperm injection: a powerful tool to overcome fertilization failure” Fertil Steril 65(5):899-908).
Additionally, many assisted reproduction clinics have found that the use of assisted hatching, the removal of a portion of the glycoprotein coating to facilitate embryo escape from the glycoprotein coat, offers the chance of a positive reproductive outcome to those women who produce embryos with impaired zona pellucidas (Meldrum D R, et al. (1998) “Assisted hatching reduces the age-related decline in IVF outcome in women younger than age 43 without increasing miscarriage or monozygotic twinning.” J Assist Reprod Genet. 15(7):418-21; Magli M C, et al. (1998) “Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching” Hum Reprod 13(5):1331-5).
More recent developments in the animal husbandry field report that somatic cell nuclei can be used as nuclear donors in nuclear transfer (Campbell, K. H. S. et al. (1996) “Sheep cloned by nuclear transfer from a cultured cell line” Nature 380, 64-66; Heyman Y, et al. (1998) “Cloning in cattle: from embryo splitting to somatic nuclear transfer.” Reprod Nutr Dev 38(6):595-603; Loi P, et al. (1998) “Embryo transfer and related technologies in sheep reproduction.” Reprod Nutr Dev 38(6):615-28). The technique of nuclear transfer includes several demanding aspects, two of which are the enucleation, or removal, of the genetic material from the recipient oocyte and the deposition of a donor nucleus in the enucleated oocyte.
Recent early stage research has shown that infertility for some women can be ameliorated by the transfer of a small quantity of cytoplasm taken from a donor oocyte from another woman, presumably one without any cytoplasmic deficiencies (Lanzendorfise; Mayer J F; Toner J, Oehningers, Saffan D S, Muashers (1999) “Pregnancy following transfer of ooplasm from cryopreserved-thawed donor oocytes into receipient oocytes” Fertility and Sterility 74(3):575-7).
The rigors of the physical manipulation of these cells during the generation of transgenic animals, intracytoplasmic sperm injection, assisted hatching, enucleation, nuclear transfers and cytoplasmic transfer as well as the sheer enormity of the demand that these procedures place on technical staff represents two of the main reasons for failure. Thus, any improvements to these procedures which result in higher rates of success as well as increased capacity for processing is of great value.